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CVI Accepts, published online ahead of print on 30 January 2008
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Clin. Vaccine Immunol. doi:10.1128/CVI.00412-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Target peptide sequence within infectious HIV-1 does not ensure envelope-specific T-helper cell re-activation: influences of cysteine protease and gamma-interferon induced thiol reductase activities

Robert Sealy, Wendy Chaka, Sherri Surman, Scott Brown, Peter Cresswell, and Julia L. Hurwitz*

Departments of Infectious Diseases and Immunology, St Jude children's Research Hospital, 332N Lauderdale, Memphis, TN 38105; Department of Immunobiology, Yale University School of Medicine, HHMI, 300 Cedar St. New Haven, CT 06520; Department of Pathology, Health Science Center, University of Tennessee, Memphis TN, 38163

* To whom correspondence should be addressed. Email: julia.hurwitz{at}stjude.org.


   Abstract

Recent studies have shown that the presence of a robust HIV-1-specific T-cell response may not be sufficient to prevent or control HIV-1 infection. Here we examined envelope-specific, MHC class II-restricted murine T-cell hybridomas for responsiveness to splenic antigen presenting cells exposed to HIV-1-infected GHOST cells. IL-2 assays showed that the presence of a peptide within HIV-1 did not ensure re-activation of peptide-specific T-cells. Further experiments defined the impact of gamma-interferon-induced thiol-reductase and cysteine proteases on the processing of HIV-1 peptides. Results highlight potential influences of peptide context on T-cell re-activation by HIV-1 and encourage continued study of antigen processing as support for improved vaccine design.







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